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目的:制备多西他赛长循环脂质体,并评价大鼠尾静脉给药的药动学特性。方法:采用薄膜分散-挤出法制备多西他赛长循环脂质体,并对其粒径分布、Zeta电位和微观形态进行表征。将12只Wistar大鼠随机分为多西他赛注射液组和多西他赛长循环脂质体组,尾静脉给药剂量均为7.5 mg·kg~(-1),采用HPLC法测定大鼠血中多西他赛的药物浓度,采用3P97程序计算多西他赛大鼠体内药动学参数。结果:多西他赛长循环脂质体平均粒径为(109.2±28.6)nm,Zeta电位为(~(-1)5.8±2.7)m V。多西他赛注射液和多西他赛长循环脂质体在大鼠体内的t_(1/2(α))分别为(0.19±0.05)h和(0.36±0.07)h;t_(1/2(β))分别为(1.82±0.33)h和(17.93±1.37)h;AUC0-t分别为(4.42±0.76)μg·ml~(-1)·h~(-1)和(33.73±3.52)μg·ml~(-1)·h~(-1)。结论:多西他赛长循环脂质体与市售多西他赛注射液相比,延长了药物在血浆中的滞留时间,能达到长循环目的。
OBJECTIVE: To prepare long-circulating liposomal docetaxel and evaluate the pharmacokinetics of the tail vein in rats. Methods: Docetaxel long circulating liposomes were prepared by membrane dispersion-extrusion method. Their particle size distribution, Zeta potential and microscopic morphology were characterized. Twelve Wistar rats were randomly divided into docetaxel injection group and docetaxel long-circulating liposome group. The dosage of tail vein was 7.5 mg · kg -1, The concentration of docetaxel in rat blood was calculated using the 3P97 program for the pharmacokinetic parameters in docetaxel rats. RESULTS: The average particle size of long circulating liposomes in docetaxel group was (109.2 ± 28.6) nm and the Zeta potential was (-1.8 ± 2.7) mV. The values of t_ (1/2) in docetaxel injection and docetaxel long circulating liposomes in rats were (0.19 ± 0.05) h and (0.36 ± 0.07) h, respectively; t_ (1 / (1.82 ± 0.33) h and (17.93 ± 1.37) h, respectively; AUC0-t was (4.42 ± 0.76) μg · ml -1 · h -1 and (33.73 ± 3.52) μg · ml -1 · h -1. CONCLUSION: Docetaxel long circulating liposomes prolong the residence time of the drug in plasma compared with the commercial injection of docetaxel and achieve the purpose of long circulation.